Preliminary studies in the model organism Drosophila melanogaster provide evidence for developmental variation due to interplay between the mother and the zygote (offspring) for the control of early events in embryogenesis. This interplay could to be based on zygotic resistance to maternal enforcement of Notch signaling in order to restrict the opportunity for zygotic cells to become germ cells. From a Darwinian perspective the germ cell would be the default fate. Activation of Notch signaling would promote adoption of the alternate somatic cell fate on which development depends. The mother and the zygote appear to use mRNA 3'UTR based mechanisms to regulate interplay. The goal of experiments described in this R21 proposal is to test for evidence of mother-zygote interplay. This goal will be achieved by testing the hypothesis that the mother and the zygote dynamically control Notch signaling in early embryogenesis events through sequences in the 3'UTR of mRNAs. Experiments are designed under three specific aims: (1) use the power of Drosophila genetics to test predictions from mother-zygote interplay in germ cell-somatic cell fate specification and three other early embryogenesis events;(2) use SNPs and molecular methods on wild type and genetically manipulated embryos to test predictions of changes in the expression profile of a sample of Notch pathway genes when their maternal or the zygotic component is removed;and (3) use an analytical method to determine if the sample of Notch pathway genes manifest patterns of sequence variation in the 3'UTR predicted from mother-offspring interplay. Early embryogenesis events can affect development more profoundly than later events and the Notch pathway functions are similar in all developmental events. Thus, mother-offspring interplay has the potential to impact a wide range of biological processes including cell fate specification, complex developmental diseases, regulation of stem cell differentiation, and assisted reproductive technology- based human pregnancy. A message that might emerge for this study is that in order to fully understand these processes it might be necessary to adapt game theoretic analysis and other analytical tools developed by population and evolutionary biologists. PUBLIC HEALTH RELEVANCE: Interaction between products of the maternal and zygotic genomes when they first meet could control many aspects of early fetal development. Variation in this interaction or its perturbation by genetic and environmental factors could determine the normal spectrum of developmental variation or development of early onset diseases. This study will begin to dissect the principles underlying maternal-zygotic interactions and identify key factors involved.